Analyses of in vivo neuroprotective role of STB/HAP1 against autonomic and motoneuron degeneration in the central and peripheral nervous system
Project/Area Number |
22K06792
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 48010:Anatomy-related
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Research Institution | Yamaguchi University |
Principal Investigator |
イスラム エムディノビウル 山口大学, 大学院医学系研究科, 講師 (80759671)
|
Co-Investigator(Kenkyū-buntansha) |
篠田 晃 山口大学, 大学院医学系研究科, 教授 (40192108)
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Project Period (FY) |
2022-04-01 – 2025-03-31
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Project Status |
Granted (Fiscal Year 2022)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2024: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | HAP1 / Stigmoid body / Motor neuron / Autonomic neuron / Motoneuron / Neurodegeneration |
Outline of Research at the Start |
Stigmoid body (STB)/huntingtin-associated protein 1 (HAP1) can protect neurodegenerative apoptosis in vitro. In this study, we will examine the changes of autonomic neurons and their functions using our recently generated HAP1-KO mice, and will elucidate the differences in motor function behavior test battery between aged-wild-type mice and aged-motor-neuron-specific HAP1-TG mice that we genetically engineered. The outcomes of this study may shed light on yet-to-be-uncovered new diagnostic or therapeutic applications for certain neurodegenerative diseases.
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Outline of Annual Research Achievements |
In the first year of our study, we clarified the neuroanatomical distribution of STB/HAP1 in the brainstem of adult mice. We also elucidated the relationships of STB/HAP1 with ChAT, with particular emphasis on autonomic and motor neurons. Our results suggest that cranial nerve motor nuclei might be more vulnerable to neurodegenerative stresses than STB/HAP1-expressing brainstem nuclei. In addition, we clarified the STB/HAP1 expression in the enteric and tongue autonomic ganglia.
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Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
We have completed our first objective, which includes the relationships of STB/HAP1 with ChAT in the brainstem. We have published our data in peer-reviewed journals.
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Strategy for Future Research Activity |
1. We will clarify the immunohistochemical relationships of STB/HAP1 with the causal agents of certain neurodegenerative diseases in vivo. 2. We will examine STB/HAP1-expression in autonomic ganglion and determine the autonomic neuron number changes in the CNS/PNS of HAP1-KO mice. Furthermore, we will compare autonomic function-related behavioral test batteries between wild-type and HAP1-KO mice. 3. Aged mouse is an excellent model to examine the vulnerability to motor neuron degeneration. We will also determine the changes in motor neuron number motor function-related behavioral test battery comparison between aged-wild type and aged-HAP1-TG mice. 4. The microbiota/gut-and-brain axis is an emerging and widely accepted concept. STB/HAP1 might affect microbiota colonization in the intestine, jeopardizing the neurodegeneration in ENS and CNS. Using HAP1-KO mice, we will examine the effects of STB/HAP1 on enteric neurons and the composition of gut microbiota.
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Report
(1 results)
Research Products
(11 results)